CA2537336C - Multi-arm polymer prodrugs - Google Patents
Multi-arm polymer prodrugs Download PDFInfo
- Publication number
- CA2537336C CA2537336C CA2537336A CA2537336A CA2537336C CA 2537336 C CA2537336 C CA 2537336C CA 2537336 A CA2537336 A CA 2537336A CA 2537336 A CA2537336 A CA 2537336A CA 2537336 C CA2537336 C CA 2537336C
- Authority
- CA
- Canada
- Prior art keywords
- prodrug
- polymer
- polymer prodrug
- poly
- armed
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229920000642 polymer Polymers 0.000 title claims abstract description 241
- 229940002612 prodrug Drugs 0.000 title claims abstract description 126
- 239000000651 prodrug Substances 0.000 title claims abstract description 126
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 24
- -1 poly(alkylene glycol Chemical compound 0.000 claims description 123
- 229960004768 irinotecan Drugs 0.000 claims description 83
- 229920001223 polyethylene glycol Polymers 0.000 claims description 63
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 62
- 239000000203 mixture Substances 0.000 claims description 55
- 206010028980 Neoplasm Diseases 0.000 claims description 54
- 125000004429 atom Chemical group 0.000 claims description 54
- 229940127093 camptothecin Drugs 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 31
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 29
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 27
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims description 13
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- 125000000547 substituted alkyl group Chemical group 0.000 claims description 8
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 5
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- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
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- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
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- 229920002125 Sokalan® Polymers 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
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- 229920001897 terpolymer Polymers 0.000 claims description 3
- 150000003573 thiols Chemical group 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims 2
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 239000013543 active substance Substances 0.000 abstract description 120
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- 238000001727 in vivo Methods 0.000 abstract description 9
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
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- 208000029742 colonic neoplasm Diseases 0.000 description 19
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- 238000011717 athymic nude mouse Methods 0.000 description 16
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- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 13
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
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- RFNSXSSACWHHMN-UHFFFAOYSA-N 4-benzyl-1,2-dihydrotriazol-5-one Chemical compound N1N=NC(CC=2C=CC=CC=2)=C1O RFNSXSSACWHHMN-UHFFFAOYSA-N 0.000 description 6
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Landscapes
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JP (4) | JP5632119B2 (ja) |
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SI (1) | SI1675622T1 (ja) |
WO (1) | WO2005028539A2 (ja) |
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US20060177416A1 (en) | 2003-10-14 | 2006-08-10 | Medivas, Llc | Polymer particle delivery compositions and methods of use |
US8394813B2 (en) | 2000-11-14 | 2013-03-12 | Shire Llc | Active agent delivery systems and methods for protecting and administering active agents |
US7169752B2 (en) * | 2003-09-30 | 2007-01-30 | New River Pharmaceuticals Inc. | Compounds and compositions for prevention of overdose of oxycodone |
US20060014697A1 (en) * | 2001-08-22 | 2006-01-19 | Travis Mickle | Pharmaceutical compositions for prevention of overdose or abuse |
US8133881B2 (en) | 2003-01-13 | 2012-03-13 | Shire Llc | Carbohydrate conjugates to prevent abuse of controlled substances |
KR20120073370A (ko) * | 2003-09-17 | 2012-07-04 | 넥타르 테라퓨틱스 | 다분지형 고분자 전구약물 |
US8394365B2 (en) | 2003-09-17 | 2013-03-12 | Nektar Therapeutics | Multi-arm polymer prodrugs |
US20070160622A1 (en) * | 2005-12-07 | 2007-07-12 | Medivas, Llc | Method for assembling a polymer-biologic delivery composition |
US9492400B2 (en) | 2004-11-04 | 2016-11-15 | Massachusetts Institute Of Technology | Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals |
RU2404980C2 (ru) * | 2005-05-11 | 2010-11-27 | Ниппон Каяку Кабусики Кайся | Полимерное производное антиметаболита цитидина |
US9346029B2 (en) | 2005-06-06 | 2016-05-24 | The University Of British Columbia | Polymer-based serum albumin substitute |
US8728493B2 (en) | 2005-06-17 | 2014-05-20 | Nektar Therapeutics | Polymer based compositions and conjugates of non-steroidal anti-inflammatory drugs |
US8445007B2 (en) | 2005-09-22 | 2013-05-21 | Medivas, Llc | Bis-(α-amino)-diol-diester-containing poly (ester amide) and poly (ester urethane) compositions and methods of use |
EP1933881B1 (en) * | 2005-09-22 | 2019-03-13 | Medivas, LLC | Solid polymer delivery compositions and methods for use thereof |
WO2007070682A2 (en) | 2005-12-15 | 2007-06-21 | Massachusetts Institute Of Technology | System for screening particles |
US9603941B2 (en) * | 2006-01-24 | 2017-03-28 | Minghui Chai | Method of preparing dendritic drugs |
US7671067B2 (en) * | 2006-02-09 | 2010-03-02 | Enzon Pharmaceuticals, Inc. | Treatment of non-hodgkin's lymphomas with multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamtothecin |
US7462627B2 (en) * | 2006-02-09 | 2008-12-09 | Enzon Pharmaceuticals, Inc. | Multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamptothecin for treatment of breast, colorectal, pancreatic, ovarian and lung cancers |
TWI426905B (zh) * | 2006-02-09 | 2014-02-21 | Enzon Pharmaceuticals Inc | 用於乳癌、大腸直腸癌、胰臟癌、卵巢癌及肺癌之治療的7-乙基-10羥喜樹鹼之多臂聚合性共軛物 |
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- 2004-09-17 KR KR1020127015575A patent/KR20120073370A/ko not_active Application Discontinuation
- 2004-09-17 EP EP04784560.7A patent/EP1675622B1/en not_active Expired - Lifetime
- 2004-09-17 DK DK04784560.7T patent/DK1675622T3/en active
- 2004-09-17 CA CA2537336A patent/CA2537336C/en not_active Expired - Lifetime
- 2004-09-17 US US10/943,799 patent/US7744861B2/en active Active
- 2004-09-17 PL PL04784560T patent/PL1675622T3/pl unknown
- 2004-09-17 PT PT47845607T patent/PT1675622T/pt unknown
- 2004-09-17 SI SI200432402T patent/SI1675622T1/sl unknown
- 2004-09-17 EP EP13164490.8A patent/EP2626083A1/en not_active Withdrawn
- 2004-09-17 AU AU2004274489A patent/AU2004274489B2/en not_active Ceased
- 2004-09-17 WO PCT/US2004/030720 patent/WO2005028539A2/en active Application Filing
- 2004-09-17 JP JP2006527105A patent/JP5632119B2/ja not_active Expired - Fee Related
- 2004-09-17 ES ES04784560.7T patent/ES2629696T3/es not_active Expired - Lifetime
- 2004-09-17 KR KR1020067007403A patent/KR101200729B1/ko active IP Right Grant
- 2004-09-17 HU HUE04784560A patent/HUE036290T2/hu unknown
- 2004-09-17 BR BRPI0414017A patent/BRPI0414017B8/pt not_active IP Right Cessation
- 2004-09-17 CN CN2004800268096A patent/CN1852740B/zh not_active Expired - Fee Related
- 2004-09-17 LT LTEP04784560.7T patent/LT1675622T/lt unknown
- 2004-09-17 CN CN201110070872.1A patent/CN102172405B/zh not_active Expired - Fee Related
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2008
- 2008-02-11 US US12/069,727 patent/US20080194612A1/en not_active Abandoned
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2010
- 2010-02-22 US US12/709,800 patent/US8263062B2/en not_active Expired - Fee Related
- 2010-03-19 US US12/728,072 patent/US8318145B2/en not_active Expired - Lifetime
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2011
- 2011-05-24 AU AU2011202402A patent/AU2011202402B2/en not_active Ceased
- 2011-06-21 JP JP2011137790A patent/JP6166014B2/ja not_active Expired - Fee Related
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2014
- 2014-06-10 JP JP2014119823A patent/JP2014196321A/ja active Pending
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2017
- 2017-03-13 JP JP2017047691A patent/JP2017119706A/ja active Pending
- 2017-07-17 HR HRP20171094TT patent/HRP20171094T1/hr unknown
- 2017-08-17 CY CY20171100875T patent/CY1119303T1/el unknown
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